Universität zu Köln

Tsakmaklis, Anastasia ORCID: 0000-0001-5380-3614 (2024). The Microbial Mediators: Investigating Microbiome-Driven Responses in Cancer Therapy. PhD thesis, Universität zu Köln.

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Abstract

The present dissertation explores the critical role of the human microbiota in the context of cancer. With an estimated 19.3 million new cases and nearly 10 million deaths globally in 2020, cancer represents a major global health challenge. In recent years, the study of the human microbiome has emerged as a frontier in biomedical research, revealing its crucial role in the development and treatment of several tumor entities. The research projects of this cumulative dissertation concentrate on the role of the microbiota (intestinal and cervical, respectively) in melanoma and cervical cancer and shed further light on how cancer therapy influences the microbiota and vice versa. The publication on cutaneous melanoma indicates that specific bacterial populations in the intestine are associated with the response to immune checkpoint inhibitor therapy. These correlations suggest that microbiome profiling could potentially serve as a basis for personalized treatment options. Furthermore, with a combination of two microbiome features and one immune feature, we were able to predict response to immunotherapy already before the initiation of the therapy. As it is still not fully understood why only some patients benefit from immune checkpoint inhibitor therapy, this is an important finding. In the publication on cervical cancer, we investigated the cervical microbiota’s response to chemoradiation therapy. Although the alpha and beta diversity of the cervical microbiota remains relatively stable, the total bacterial load decreases significantly post-treatment. Furthermore, we observed inter-individual differences in the composition of the cervical microbiota in our cohort already before and after treatment with chemoradiation. Beyond the two studies, the dissertation discusses the broader implications of microbiome research in enhancing cancer therapy efficacy. Potential strategies for future therapeutic interventions aiming at altering the patients’ microbiota, such as the use of probiotics and microbiota transfer techniques, are currently under investigation. Overall, this work makes a relevant contribution to the evolving field of microbiome research in cancer therapy, presenting new pathways for enhancing the effectiveness of treatment protocols and thus paving the way for innovative, microbiome-based personalized treatment approaches that may subsequently lead to better outcomes for patients.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Tsakmaklis, Anastasia anastasia.tsakmaklis@uk-koeln.de orcid.org/0000-0001-5380-3614 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-732654
Date:	2024
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Innere Medizin > Klinik I für Innere Medizin - Hämatologie und Onkologie
Subjects:	Life sciences Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Microbiome English Immune Checkpoint Inhibitor English Cancer English
Date of oral exam:	19 July 2024
Referee:	Name Academic Title Seifert, Harald Prof. Dr. Kahkar, Hamid Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/73265